Recombinant Mouse 5-hydroxytryptamine receptor 7 (Htr7)
Description
Core Signaling Pathways
The 5-HT7 receptor couples to adenylate cyclase (AC) via Gαs proteins, increasing intracellular cAMP levels . This signaling cascade is critical for diverse physiological processes:
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Vascular and gastrointestinal smooth muscle relaxation
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Thermoregulation and circadian rhythm modulation
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Immune regulation (e.g., dendritic cell migration, IgA+ B cell differentiation)
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Cognitive functions (learning, memory, and hippocampal-dependent processes)
Immunological and Pathological Roles
Recombinant Htr7 has been instrumental in elucidating serotonin’s immunomodulatory effects:
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Dendritic cell homing: Htr7 activation by enteric neuron-derived serotonin enhances lamina propria dendritic cell retention via CCR7 upregulation, promoting IgA+ B cell differentiation .
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Fibrotic responses: Htr7-PKA signaling in macrophages drives TGFβ1 production, contributing to collagen deposition in bleomycin-induced skin fibrosis models .
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Cancer resistance: Overexpression of Htr7 in pancreatic ductal adenocarcinoma (PDAC) cells correlates with gemcitabine resistance via EZH2-TPH1-5-HT7 axis activation .
Agonists and Antagonists
Recombinant Htr7 has been used to characterize selective ligands, enabling precise modulation of receptor activity:
Structure-Activity Relationships (SAR)
Key structural features influencing Htr7 ligand affinity include:
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Halogen substituents (e.g., iodine, bromine) at the 5-position of indole derivatives, enhancing binding affinity .
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Imidazole cores in low-basicity scaffolds (e.g., AGH-107), which improve metabolic stability and blood-brain barrier permeability .
Neurological and Cognitive Studies
Recombinant Htr7 has been pivotal in understanding serotonin’s role in:
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Learning and memory: Htr7 knockout mice show deficits in spatial memory tasks (e.g., Barnes maze), suggesting receptor involvement in hippocampal allocentric processing .
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Rett and Fragile X syndromes: Agonists like AS-19 improve neuronal excitability in preclinical models .
Immune and Inflammatory Disorders
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Irritable bowel syndrome: Htr7 antagonists reduce visceral hypersensitivity in mouse models by modulating enteric nerve fiber activity .
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Skin fibrosis: Htr7-deficient mice exhibit reduced macrophage infiltration and collagen deposition in dermal fibrosis models .
Oncology and Drug Resistance
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Pancreatic cancer: Htr7 overexpression in gemcitabine-resistant PDAC cells is linked to EZH2-mediated epigenetic regulation, enabling targeted therapeutic strategies .
Challenges and Future Directions
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Isoform-Specific Signaling: Differences in receptor internalization (e.g., 5-HT7(d)) may require isoform-specific recombinant models for accurate pharmacological profiling .
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Species-Specific Variations: Mouse Htr7 exhibits distinct splice variants and tissue distributions compared to human 5-HT7, necessitating cross-species validation .
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Therapeutic Potential: Development of CNS-penetrant Htr7 agonists/antagonists for neurological or immune disorders remains a priority .
Product Specs
Note: We prioritize shipping the format currently in stock. However, if you have a specific format requirement, please indicate it when placing your order, and we will accommodate your request.
Note: All proteins are shipped with standard blue ice packs. If you require dry ice shipping, please communicate with us in advance as additional fees will apply.
Generally, the shelf life of the liquid form is 6 months at -20°C/-80°C. The shelf life of the lyophilized form is 12 months at -20°C/-80°C.
Target Background
- Downregulation of the 5-HT7 receptor in the medial prefrontal cortex (mPFC) improves neonatal administration of phencyclidine-induced attentional deficits and impulsive-like overresponding and exacerbates compulsivity. These findings suggest that 5-HT7R is involved in the cognitive outcomes of schizophrenia-like symptoms, mirroring human observations. PMID: 29278697
- The present study demonstrated that acute heroin administration resulted in notable disruptions in attention, impulsivity, and motivation in mice. PMID: 29155092
- The underlying molecular mechanisms involve 5-HT7R-mediated activation of MMP-9, leading to CD44 cleavage followed by Cdc42 activation. PMID: 28564597
- The findings of this study provide evidence for the essential role of the 5HT7R in the acquisition of an allocentric strategy and the ability to learn both strategies concurrently. PMID: 27939340
- The data from this study suggest that the 5-HT7R-mediated structural reorganization during postnatal development plays a crucial role in the development and plasticity of forebrain areas such as the cortex and striatum. PMID: 28122114
- This study demonstrates that 5-HT7 is expressed in the liver in vivo and in vitro in CCl4-induced damage, and that 5-HT7 receptor agonist, but not the antagonist, exhibits a hepatoprotective effect against liver fibrosis. PMID: 28043031
- 5-HT7 is required for multiple actions of serotonin in the mammary glands. PMID: 25664318
- Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. Acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1, as did the development of atopic dermatitis. PMID: 26074006
- Blockade of 5-HT7R Results in Increased Severity of Chronic DSS-induced Colitis. PMID: 25072499
- Data suggest that 5-HT7R tonically modulates cognitive processes involved in consolidation performances in object recognition. PMID: 23995300
- These results indicate that 5-HT receptors are functionally expressed in a subpopulation of substantia gelatinosa neurons and that activation of 5-HT receptors plays a significant role in modulating orofacial nociceptive processing. PMID: 24516875
- The results provide evidence that lurasidone can act as a 5-HT7 receptor antagonist and offer a possible explanation for its antidepressant effect. PMID: 23416039
- Colitis severity was significantly lower in 5-HT7(-/-) mice. PMID: 23554310
- The 5-HT7 receptor is functionally involved in the development of stress adaptation.[review] PMID: 23012886
- Activation of the serotonin 5-HT7 receptor promotes synaptogenesis and enhances synaptic activity in hippocampal neurons at early postnatal stages. PMID: 22378867
- 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor PMID: 12529502
- Binding sites consistent with mRNA distribution with highest densities found in anterior thalamic nuclei. PMID: 15026130
- The results indicate an important role for the 5-HT(7) receptor in contextual hippocampal-dependent learning and suggest a possible neuronal correlate for such a role is present within the CA1 region of the hippocampus. PMID: 15078565
- Data demonstrate distinct roles for 5-HT7R/G12 signaling pathways in neurite outgrowth and retraction PMID: 16120784
- The results, obtained with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of 5-HT7 receptors to spinal locomotor rhythmogenesis in vivo. PMID: 16836640
- The 5-HT7 receptor is significant for behaviors affected by antidepressants, suggesting its potential relevance as a target for treating obsessive-compulsive disorder. PMID: 17267119
- Cloning, genomic organization, and functionality of 5-HT7 receptor splice variants from mouse brain are reported. PMID: 18793707
- 5-HT(7) receptor deletion augments the effect of various SSRIs on REM sleep suppression, and this effect is distinct from those mediated via 5-HT(1A) receptors. PMID: 18948124
- The present study has shown that the 5-HT7 receptor is important for allocentric spatial memory. PMID: 19447277
- These results suggest that spinal 5-HT7 receptors are necessary for the production and coordination of 5-HT-induced locomotor-like activity in neonatal mice and are crucial for coordinating voluntary locomotion in adult mice. PMID: 19458153
